Inhibitor development and clinical characteristics in children with severe hemophilia A in the ATHN 8 US cohort study

Blood Vessels, Thrombosis & Hemostasis Pub Date : 2025-06-16 DOI:10.1016/j.bvth.2025.100082

Courtney D. Thornburg , H. Marijke van den Berg , Martin Chandler , Lynn Malec , Matthew Manuel , Carrie O’Neill , Michael Recht , Elizabeth Taggart , Shannon L. Carpenter

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Abstract

Clotting factor concentrate (CFC), used to treat and prevent bleeding in hemophilia, is rendered ineffective if clotting factor neutralizing antibodies (inhibitors) develop. Inhibitors occur most often in children, early in treatment. The American Thrombosis and Hemostasis Network (ATHN) 8: US Cohort Study of Previously Untreated Patients (PUPs) with Congenital Hemophilia, conducted in children born in 2010 to 2020 with severe or moderate hemophilia, was designed to determine the percentage of participants who developed a confirmed, clinically significant inhibitor within the first 50 CFC exposure days (EDs). Cox proportional hazards models were used to evaluate risk factors for inhibitor development in PUPs with severe hemophilia A (HA). A total of 171 males with severe HA enrolled: 39 (22.8%) developed an inhibitor, 30 (17.5%) developed a high-titer inhibitor, and 9 (5.3%) developed a low-titer inhibitor; 82.1% within 20 EDs. Product exposure at <1 month (hazard ratio [HR], 2.57; 95% confidence interval [CI], 1.22-5.44), large structural changes (HR,16.59; 95% CI, 1.94-142.20), and nonsense variants (HR, 12.53; 95% CI, 1.41-111.49) were associated with inhibitor development. Overall, inhibitor development remains a significant CFC complication especially in the first 10 to 20 EDs. Further study should evaluate the impact of new treatments on inhibitor rates and age at inhibitor development and identify strategies to reduce inhibitor development.

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ATHN 8美国队列研究中严重血友病A患儿抑制剂的发展和临床特征

摘要浓缩凝血因子（CFC）用于治疗和预防血友病出血，如果产生凝血因子中和抗体（抑制剂），则会失效。抑制剂最常见于儿童，在治疗早期。美国血栓和止血网络（ATHN） 8：先天性血友病未治疗患者（PUPs）的美国队列研究，在2010年至2020年出生的患有严重或中度血友病的儿童中进行，旨在确定在前50个CFC暴露天（EDs）内发展出确认的临床显著抑制剂的参与者的百分比。采用Cox比例风险模型评估严重血友病A （HA）患儿抑制剂发展的危险因素。共有171名患有严重血凝素的男性入组：39名（22.8%）出现抑制剂，30名（17.5%）出现高效价抑制剂，9名（5.3%）出现低效价抑制剂；82.1%在20个ed内。产品暴露1个月(危险比[HR]， 2.57；95%可信区间[CI]， 1.22-5.44)，结构变化较大(HR,16.59；95% CI, 1.94-142.20)和无意义变异(HR, 12.53；95% CI, 1.41-111.49)与抑制剂发展相关。总的来说，抑制剂的发展仍然是一个重要的CFC并发症，特别是在前10到20例ed中。进一步的研究应该评估新疗法对抑制剂率和抑制剂发展年龄的影响，并确定减少抑制剂发展的策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Blood Vessels, Thrombosis & Hemostasis

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